AB0474 REAL-WORLD SINGLE CENTER USE OF UPADACITINIB IN RHEUMATOID ARTHRITIS PATIENTS, INCLUDING THOSE REFRACTORY TO FIRST-GENERATION JAK INHIBITORS
Authors: M. Kamiya, S. Mori, K. Yamazaki, N. Oka, N. Shoukaku, D. Togawa
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> In practice, bDMARDs and subsequent first-generation JAK inhibitors (JAKi) have significantly improved the management of rheumatoid arthritis (RA), but there are still patients refractory or intolerant to multiple b/tsDMARDs. The fact that first-generation JAKi inhibit more than one JAK molecule has given rise to hopes that second-generation JAKi with enhanced kinase selectivity may maximize efficacy and enable a safer profile. Although a matched-adjusted indirect comparative study, differences in efficacy between some of the two JAKi drugs have been demonstrated, suggesting that second-generation JAKi may be effective for RA patients who are intolerant or have inadequate responses to first-generation JAKi. <h3>Objectives</h3> We evaluated the real-world course of upadacitinib (UPA), a second-generation JAKi, in a single-center cohort of RA patients, including refractory patients with resistance to first-generation JAK inhibitors. <h3>Methods</h3> All RA patients who started UPA between May 2021 and June 2022, including those who had previously received tofacitinib (TOF) and/or baricitinib (BAR), were eligible for the study. Kaplan-Meier survival rates were calculated based on ineffectiveness or intolerance as the reason for discontinuation. DAS28-ESR score, PRO (VAS for pain and stiffness), and patient satisfaction on a 7-point scale were recorded at baseline, 3 months, and 6 months. In addition, RF factor antibody titers before and after UPA administration, concomitant MTX and PSL doses, and UPA dose at 6 months were recorded. The above items were evaluated in subgroups of JAKi-non-use cases and the number of JAKi used in the past. In addition, reasons for discontinuation of administration were also investigated. <h3>Results</h3> UPA was administered to 122 patients, 85.2% of whom were female, age (S.D.) 69.7 (11.9) years, weight 52.5 (8.4) kg, duration of RA (S.D.) 15.8 (10.3) years, and 97.5% of whom were RF or anti-CCP antibody positive. A median of 2.5 bDMARDs had been administered, including 37 patients who received IL-6 inhibitors. 52 patients (1st JAKi group) did not use any JAKi, 51 patients (2nd JAKi group) used one type (15 TOF, 36 BAR), and 19 patients (3rd JAKi group) used two types. Survival rates at 6 months were 92.3%, 90.2%, and 94.7% (P=0.83) in each group, and none of the 82 patients who could be followed for more than 12 months discontinued between 6 and 12 months. The mean DAS28-ESR (S.D.) at baseline was 3.91 (0.78) overall, but significantly improved to 2.79 (0.82) at 6 months (P&lt;0.05). 67.3%, 70.6% and 47.4% of patients in each group had low disease activity. The VAS for pain and stiffness improved significantly in the 1st and 2nd JAKi groups, including treatment satisfaction. 88% of patients had decreased RF factor antibody titer. 62.5% of patients received UPA less than 7.5 mg/day at 6 months, including those who received UPA every other day. The rate of concomitant use of PSL (&lt;5 mg) remained unchanged at 10.7%, and the rate of MTX decreased from 27.7% to 7.1%, mainly in the 1st JAKi group. 4 patients developed herpes zoster within 6 months and UPA was resumed after a temporary suspension. 2 patients discontinued UPA due to inadequate efficacy and 8 due to adverse events. Adverse events requiring hospitalization were bacterial pneumonia, putaminal hemorrhage, and sudden death with suspected acute myocardial infarction. <h3>Conclusion</h3> UPA was effective in RA patients, including first-generation JAKi-resistant patients, with few cases of discontinuation due to inadequate efficacy. Although some Japanese patients taper off UPA due to their light weight, advanced age, or complications, more than 60% of patients maintained efficacy with UPA at 7.5 mg/day or less, suggesting that taper-off is feasible. After disease activity decreased, tapering or discontinuation of concomitant MTX was prioritized, but there were no cases of apparent flares, again confirming the efficacy of UPA alone. In addition to the long-term safety of UPA, head-to-head between JAKi and JAKi to bDMARDs should be considered in the future. <h3>REFERENCES:</h3> NIL. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.